From seeds to survival rates: investigating Linum usitatissimum's potential against ovarian cancer through network pharmacology.

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan-Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics.

In-silico design and synthesis of N9-substituted ß-Carbolines as PLK-1 inhibitors and their in-vitro/in-vivo tumor suppressing evaluation.

A new series of ß-Carboline/Schiff bases was designed, synthesized, characterised and biologically evaluated as inhibitors of PLK-1. The synthesized compounds exhibited strong to moderate cytotoxic activities against NCI-60 panel cell assay. Compound SB-2 was the most potent, particularly against colon with GI50 of 3-45 µM on NCI-60 panel cell lines. SB-2 selectively inhibited PLK-1 at 15 µM on KinomeScan screening. It also showed a dose-dependent cell cycle arrest at S/G2 phase on HCT-116 and induced apoptosis by the activation of procaspase-3 and cleaved PARP. Further, the antitumor studies on DLA and EAC model revealed that SB-2, at 100 mg/kg/bd.wt significantly increased their average lifespan. Further, a decrease in the body weight of the tumor-bearing mice was also observed when compared to the tumor controlled mice. SB-2 thus shows good potential as antitumor agent.

Potential Pharmacological Inhibitors of Pim Kinase Under Clinical Trials.

Pim kinases, also known as Serine/Threonine kinases, are intensively studied protein drug targets in cancer research. They play crucial role in the regulation of signal transduction cascades that promote cell survival, proliferation and drug resistance. Pim kinases are overexpressed in several hematopoietic and solid tumors and support in vitro/in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. Pim kinases do not have an identified regulatory domain, as they are constitutively active. They appear to be critical downstream effectors of a number of oncoproteins. When overexpressed, they mediate drug resistance to agents such as Rapamycin. X-ray crystallographic studies reveal that unlike other kinases, Pim kinases have a hinge region, which forms a unique binding pocket for ATP, offering a target for a large number of potent small-molecule Pim kinase inhibitors. Combination therapy of Pim kinase inhibitors with chemotherapeutic and other kinase modulators seems to produce an additive cytotoxic effect in cancer cells. Though clinical trials have been carried out on the first Pim inhibitory agent, SGI-1776, no concept data could be generated due to its early withdrawal. However, it has helped in accelerating the discovery of several novel Pim inhibitors in recent years. Current research on Pim kinase is expected to lead to a new generation of potent Pim kinase inhibitors with appropriate pharmacological profiles suitable for human cancer therapy in the near future. Herein, we review the synthetic route and mechanistical studies of Pim kinase inhibitors which are currently in human trials.